3d4u: Difference between revisions
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< | ==Bovine thrombin-activatable fibrinolysis inhibitor (TAFIa) in complex with tick-derived carboxypeptidase inhibitor.== | ||
<StructureSection load='3d4u' size='340' side='right'caption='[[3d4u]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3d4u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Rhipicephalus_bursa Rhipicephalus bursa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D4U FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3d4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d4u OCA], [https://pdbe.org/3d4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d4u RCSB], [https://www.ebi.ac.uk/pdbsum/3d4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d4u ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CBPB2_BOVIN CBPB2_BOVIN] Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d4/3d4u_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3d4u ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Thrombin-activatable fibrinolysis inhibitor (TAFI) is a metallocarboxypeptidase (MCP) that links blood coagulation and fibrinolysis. TAFI hampers fibrin-clot lysis and is a pharmacological target for the treatment of thrombotic conditions. TAFI is transformed through removal of its prodomain by thrombin-thrombomodulin into TAFIa, which is intrinsically unstable and has a short half-life in vivo. Here we show that purified bovine TAFI activated in the presence of a proteinaceous inhibitor renders a stable enzyme-inhibitor complex. Its crystal structure reveals that TAFIa conforms to the alpha/beta-hydrolase fold of MCPs and displays two unique flexible loops on the molecular surface, accounting for structural instability and susceptibility to proteolysis. In addition, point mutations reported to enhance protein stability in vivo are mainly located in the first loop and in another surface region, which is a potential heparin-binding site. The protein inhibitor contacts both the TAFIa active site and an exosite, thus contributing to high inhibitory efficiency. | |||
Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular link between coagulation and fibrinolysis.,Sanglas L, Valnickova Z, Arolas JL, Pallares I, Guevara T, Sola M, Kristensen T, Enghild JJ, Aviles FX, Gomis-Ruth FX Mol Cell. 2008 Aug 22;31(4):598-606. PMID:18722183<ref>PMID:18722183</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3d4u" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[ | |||
== | |||
< | |||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Rhipicephalus bursa]] | [[Category: Rhipicephalus bursa]] | ||
[[Category: Arolas | [[Category: Arolas JL]] | ||
[[Category: Aviles | [[Category: Aviles FX]] | ||
[[Category: Enghild | [[Category: Enghild JJ]] | ||
[[Category: Gomis-Ruth | [[Category: Gomis-Ruth FX]] | ||
[[Category: Guevara | [[Category: Guevara T]] | ||
[[Category: Kristensen | [[Category: Kristensen T]] | ||
[[Category: Pallares | [[Category: Pallares I]] | ||
[[Category: Sanglas | [[Category: Sanglas L]] | ||
[[Category: Sola | [[Category: Sola M]] | ||
[[Category: Valnickova | [[Category: Valnickova Z]] | ||
Latest revision as of 11:57, 30 October 2024
Bovine thrombin-activatable fibrinolysis inhibitor (TAFIa) in complex with tick-derived carboxypeptidase inhibitor.Bovine thrombin-activatable fibrinolysis inhibitor (TAFIa) in complex with tick-derived carboxypeptidase inhibitor.
Structural highlights
FunctionCBPB2_BOVIN Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThrombin-activatable fibrinolysis inhibitor (TAFI) is a metallocarboxypeptidase (MCP) that links blood coagulation and fibrinolysis. TAFI hampers fibrin-clot lysis and is a pharmacological target for the treatment of thrombotic conditions. TAFI is transformed through removal of its prodomain by thrombin-thrombomodulin into TAFIa, which is intrinsically unstable and has a short half-life in vivo. Here we show that purified bovine TAFI activated in the presence of a proteinaceous inhibitor renders a stable enzyme-inhibitor complex. Its crystal structure reveals that TAFIa conforms to the alpha/beta-hydrolase fold of MCPs and displays two unique flexible loops on the molecular surface, accounting for structural instability and susceptibility to proteolysis. In addition, point mutations reported to enhance protein stability in vivo are mainly located in the first loop and in another surface region, which is a potential heparin-binding site. The protein inhibitor contacts both the TAFIa active site and an exosite, thus contributing to high inhibitory efficiency. Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular link between coagulation and fibrinolysis.,Sanglas L, Valnickova Z, Arolas JL, Pallares I, Guevara T, Sola M, Kristensen T, Enghild JJ, Aviles FX, Gomis-Ruth FX Mol Cell. 2008 Aug 22;31(4):598-606. PMID:18722183[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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